Stereoselectivity magnesium enolate preparation

Several workers have observed aldol reactions with enolates prepared by reductive removal of an o-heteroatom from a carbonyl compound. The classic example is the Reformatsky reaction, which is reviewed in Volume 2, Chapter 1.8. Dubois and coworkers have employed this method for the preparation of magnesium enolates. An important example from this study, which stimulated much of the subsequent work on aldol stereoselectivity, is shown in equation (21). 

In order to improve the stereoselectivity of the aldol process even further, metal salts of enolate anions other than those bearing lithium have been examined. For example, both magnesium and boron enolates have been prepared. Magnesium enolates are very much like lithium enolates in their stereoselectivity, while boron enolates, where there are relatively short metal-oxygen bonds, give improved selectivity. For the boron enolates, the (Z)-enolate is generally more stable than its E)-isomer, and erythro- or 5yn-products are developed. 

S, entries 1-9). The stereoisomer ratios observed seem to be kinetic, rather than thermodynamic, since the same yield and enantiomeric excess are observed at reaction times of 3 or 60 min (Table 25, entries 3 and 4). Stereoselectivity decreases as the size of increases (entries 1,2,3 and 6). Addition of HMPA has a deleterious effect on stereoselectivity. The magnesium enolate shows excellent diastereoselectivity. Again, stereoselectivity diminishes as the size of increases (Table 25, entries 10, 11, 14 and 16) and HMPA has a detrimental effect (entry 18). The analogous thioamide was prepared and studied, but it appears to offer no advantage over the oxoamide. ... 

Thioamide enolates are also interesting substrates for the stereoselective aldol-type reactions. The aldol stereochemistry is very sensitive to the conditions of preparation of magnesium thioamide enolates and it generally gives different results depending on the procedure used. Illustrations of some aspects of the reactivity are provided in the examples presented below. 

Mukaiyama and coworkers have pioneered many routes to the total syntheses of rare carbohydrates such as the 2-amino-2-deoxypentoses [75]. In 1982, they reported that the potassium enolate derived from the magnesium salt of the (/ )-atrolactic acid derivative 85 adds to 2,3-0-isopropylidene-D-glyceraldehyde in a highly stereoselective manner giving, after alcohol protection, imine hydrolysis and amine protection, the D-arabinopentoate derivative 86 (Scheme 13.35). Further elaboration leads to 2-acetamido-2-deoxy-D-arabinose 87. In a similar fashion, starting from (5 )-atrolactic acid, 2-acetamido-2-deoxy-D-ribose 88 was prepared [76]. 

The addition of a 2-hydroxyaryl group to an aldehyde can be considered as a case of aldolization using a phenoxide instead of an enolate. Casiraghi et al used magnesium and titanium salts to prepare l-(2-hydroxyaryl)glycerols (p. 81). The stereoselectivity depends on the nature of the metal. 

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